Background: Acyclovir is used to treat herpes simplex virus disease in infants. Treatment with high-dose acyclovir, 60 mg/kg/d, is recommended; however, the safety of this dosage has not been assessed in the past 15 years, and this dosage is not currently approved for infants by the US Food and Drug Administration.
Methods: We included infants with neonatal herpes simplex virus disease treated with ≥14 days of intravenous acyclovir starting in the first 120 days of life admitted to 1 of 42 neonatal intensive care units managed by the Pediatrix Medical Group between 2002 and 2012. We determined the frequency and proportion of infants with clinical and laboratory adverse events (AEs) as well as the number and proportion of infant days with laboratory AEs occurring during acyclovir exposure.
Results: We identified 89 infants during the study period with 1658 days of acyclovir exposure. Almost all received high-dose acyclovir therapy (79/89, 89%). The most common clinical AEs were hypotension and seizure, both occurring in 9% of infants. Thrombocytopenia was the most common laboratory AE occurring in 25% of infants and on 9% of infant-days. Elevated creatinine occurred in 2% of infants and 0.2% of infant-days and no infants developed renal failure requiring dialysis. Overall, 45% of infants had ≥1 AE.
Conclusions: In this cohort of infants treated during the high-dose acyclovir era, AEs were common but usually not severe. Many of the AEs reported in this cohort may be related to the underlying infection rather than due to acyclovir exposure.
From the *Duke Clinical Research Institute, Durham, North Carolina; †Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania; ‡Department of Pediatrics, CHU Sainte Justine, §Department of Pharmacology, University of Montreal, Montreal, Quebec, Canada; ¶Department of Pediatrics, Duke University, Durham, North Carolina; and ‖Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida.
Accepted for publication September 11, 2016.
C.P.H. receives salary support for research from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR001117). D.K.B. receives support from the National Institutes of Health (NIH) (Award 2K24HD058735-06, National Center for Advancing Translational Sciences award UL1TR001117, National Institute of Child Health and Human Development contract HHSN275201000003I and National Institute of Allergy and Infectious Diseases contract HHSN272201500006I); he also receives research support from Cempra Pharmaceuticals (Subaward to HHSO100201300009C) and industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. P.B.S. receives salary support for research from the NIH (NIH-1R21HD080606-01A1) and the National Institute for Child Health and Human Development (NICHD) (HHSN275201000003I). J.E.E. receives support from the National Institute of Child Health and Human Development of the National Institutes of Health under Award Number 5T32HD060558. For the remaining authors, none was declared. This work was funded under National Institute of Child Health and Human Development (NICHD) Contract HHSN275201000003I for the Pediatric Trials Network, as well as NICHD Grant 1R25HD076475. This study used Clinical and Translational Science Award biostatistical services through the Division of Pediatric Quantitative Sciences (NIH-5UL-1RR024128-01).
The authors have no conflicts of interest to disclose.
Address for correspondence: P. Brian Smith, MD, MPH, MHS, Department of Pediatrics, Duke Clinical Research Institute, Box 17969, Durham, NC 27715. E-mail: firstname.lastname@example.org.